Tumor Immune Response in the Presence of a Cytotoxic Peptide

2018 ◽  
Vol 69 (5) ◽  
pp. 1179-1186
Author(s):  
Teodor Stefanache ◽  
Daniela Jitaru ◽  
Mihaiela Loredana Dragos ◽  
Magda Badescu ◽  
Bogdan Mihail Diaconescu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cell Metabolism ◽  
Genetic Material ◽  
High Concentrations ◽  
Cytotoxic Peptide ◽  
Ht 29

We evaluated, by the flow cytometry technique, the viability of two tumor cell lines: colorectal carcinoma (HT-29) and human A549 arcinoma incubated with the cytotoxic peptide LL-37. The results obtained for the two cell lines HT-29 and A549 are significantly different under the action of cathelicidin LL-37. At high concentrations of 20mM, cellular apoptosis was over 30% higher for colorectal adenocarcinoma line compared to that by peptide exposure. Apoptosis was also significant in low-concentration (4uM) catechidine-labeled lung cancer cells for 48 h. Also, optimization of primers was sought to evaluate gene expression for, Bcl2, IL6, IL8. Determination of gene expression for these molecular targets under the action of the cytotoxic peptide was performed in order to evaluate the immune response of tumor cells. For this purpose, the genetic material (RNA) was extracted from cell cultures and reversed in cDNA, which was subsequently amplified by the qRT-PCR technique. Evaluation of tumor cell metabolism was done by determining the gene expression for Bcl2, IL6, IL8 by the action of the cytotoxic peptides used. The cytotoxic effect of cathelicidin LL-37 for the two cell lines HT29 and A549 is supported by the decrease in IL-6 and IL-8 gene expression. The increase in Bcl2 expression for cells exposed to the action of the peptide is explained by the increase in anti-apoptotic protein synthesis that explains the fight of tumor cells for survival and proliferation.

scholarly journals Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1563
Author(s):  
María Pulido ◽  
Virginia Chamorro ◽  
Irene Romero ◽  
Ignacio Algarra ◽  
Alba S-Montalvo ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Mhc Class I ◽  
Cell Lines ◽  
Surface Expression ◽  
Tumor Cell Lines ◽  
Immune Rejection ◽  
Mhc I ◽  
Negative Tumor

The capacity of cytotoxic-T lymphocytes to recognize and destroy tumor cells depends on the surface expression by tumor cells of MHC class I molecules loaded with tumor antigen peptides. Loss of MHC-I expression is the most frequent mechanism by which tumor cells evade the immune response. The restoration of MHC-I expression in cancer cells is crucial to enhance their immune destruction, especially in response to cancer immunotherapy. Using mouse models, we recovered MHC-I expression in the MHC-I negative tumor cell lines and analyzed their oncological and immunological profile. Fhit gene transfection induces the restoration of MHC-I expression in highly oncogenic MHC-I-negative murine tumor cell lines and genes of the IFN-γ transduction signal pathway are involved. Fhit-transfected tumor cells proved highly immunogenic, being rejected by a T lymphocyte-mediated immune response. Strikingly, this immune rejection was more frequent in females than in males. The immune response generated protected hosts against the tumor growth of non-transfected cells and against other tumor cells in our murine tumor model. Finally, we also observed a direct correlation between FHIT expression and HLA-I surface expression in human breast tumors. Recovery of Fhit expression on MHC class I negative tumor cells may be a useful immunotherapeutic strategy and may even act as an individualized immunotherapeutic vaccine.

Interaction of Human Tumor Cells with Human Platelets and the Coagulation System

1983 ◽  
Vol 50 (03) ◽  
pp. 726-730 ◽  
Author(s):  
Hamid Al-Mondhiry ◽  
Virginia McGarvey ◽  
Kim Leitzel
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Human Tumor ◽  
Human Platelets ◽  
Factor Vii ◽  
Coagulation System ◽  
Breast Adenocarcinoma ◽  
Activate Factor ◽  
Tumor Cell Lines

SummaryThis paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I- labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through “the extrinsic pathway” with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to “make available” a platelet- derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.

scholarly journals Protein citrullination as a source of cancer neoantigens

2021 ◽  
Vol 9 (6) ◽  
pp. e002549
Author(s):  
Hiroyuki Katayama ◽  
Makoto Kobayashi ◽  
Ehsan Irajizad ◽  
Alejandro Sevillarno ◽  
Nikul Patel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Immune Response ◽  
Protein Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Family Members ◽  
Immunohistochemical Analysis ◽  
Cancer Cell Lines ◽  
Mhc Ii

BackgroundCitrulline post-translational modification of proteins is mediated by protein arginine deiminase (PADI) family members and has been associated with autoimmune diseases. The role of PADI-citrullinome in immune response in cancer has not been evaluated. We hypothesized that PADI-mediated citrullinome is a source of neoantigens in cancer that induces immune response.MethodsProtein expression of PADI family members was evaluated in 196 cancer cell lines by means of indepth proteomic profiling. Gene expression was assessed using messenger RNA data sets from The Cancer Genome Atlas. Immunohistochemical analysis of PADI2 and peptidyl-citrulline was performed using breast cancer tissue sections. Citrullinated 12–34-mer peptides in the putative Major Histocompatibility Complex-II (MHC-II) binding range were profiled in breast cancer cell lines to investigate the relationship between protein citrullination and antigen presentation. We further evaluated immunoglobulin-bound citrullinome by mass spectrometry using 156 patients with breast cancer and 113 cancer-free controls.ResultsProteomic and gene expression analyses revealed PADI2 to be highly expressed in several cancer types including breast cancer. Immunohistochemical analysis of 422 breast tumor tissues revealed increased expression of PADI2 in ER− tumors (p<0.0001); PADI2 protein expression was positively correlated (p<0.0001) with peptidyl-citrulline staining. PADI2 expression exhibited strong positive correlations with a B cell immune signature and with MHC-II-bound citrullinated peptides. Increased circulating citrullinated antigen–antibody complexes occurred among newly diagnosed breast cancer cases relative to controls (p=0.0012).ConclusionsAn immune response associated with citrullinome is a rich source of neoantigens in breast cancer with a potential for diagnostic and therapeutic applications.

scholarly journals A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4350
Author(s):  
Jessica Castro ◽  
Giusy Tornillo ◽  
Gerardo Ceada ◽  
Beatriz Ramos-Neble ◽  
Marlon Bravo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Tumor Cell Lines

Despite the significant advances in cancer research made in recent years, this disease remains one of the leading causes of death worldwide. In part, this is due to the fact that after therapy, a subpopulation of self-renewing tumor cells can survive and promote cancer relapse, resistance to therapies and metastasis. Targeting these cancer stem cells (CSCs) is therefore essential to improve the clinical outcome of cancer patients. In this sense, multi-targeted drugs may be promising agents targeting CSC-associated multifocal effects. We have previously constructed different human pancreatic ribonuclease (RNase) variants that are cytotoxic for tumor cells due to a non-classical nuclear localization signal introduced in their sequence. These cytotoxic RNases affect the expression of multiple genes involved in deregulated metabolic and signaling pathways in cancer cells and are highly cytotoxic for multidrug-resistant tumor cell lines. Here, we show that these cytotoxic nuclear-directed RNases are highly selective for tumor cell lines grown in 3D, inhibit CSCs’ development and diminish the self-renewal capacity of the CSCs population. Moreover, these human RNase variants reduce the migration and invasiveness of highly invasive breast cancer cells and downregulate N-cadherin expression.

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